{
  "abstract": "Background POEMS syndrome is a rare, life-threatening multisystem disease driven by clonal plasma cell proliferation and characterised by disabling neuropathy, a monoclonal plasma cell disorder and diagnostic paraneoplastic features. Although vascular endothelial growth factor (VEGF) is a key diagnostic marker and correlates with disease activity, it is not the central mediator and the specific pathomechanism for the characteristic distal sensorimotor neuropathy remains elusive. Pyridoxal 5’-phosphate (PLP), the active form of vitamin B 6, is an essential cofactor for human biological processes; its deficiency is known to cause distal sensorimotor neuropathy.Methods Following reports of B6 deficiency in POEMS syndrome, 50 sequential patients at our centre (18 active, 32 in remission) were tested for PLP deficiency between September 2023 and July 2024.Results Active POEMS patients demonstrated significantly lower plasma PLP concentrations (median 9.5 nmol/L) compared with those in treated remission (median 36 nmol/L; p<0.0001). Significant negative correlations were observed between plasma PLP and serum VEGF (r=−0.64, p<0.0001) and paraprotein concentration (r=−0.3783, p=0.0068). In nine patients, PLP levels normalised (median 8.5–37 nmol/L; p<0.002) following treatment-induced remission without B6 supplementation. Notably, two cases of (P)OEMS (POEMS features with elevated VEGF but without neuropathy) maintained normal PLP levels. Increased ratios of pyridoxic acid to PLP in active patients suggest a catabolic shift and dysfunctional B6 metabolism.Conclusions Our findings indicate a correlation between active POEMS syndrome and low plasma PLP. We hypothesise that severe PLP deficiency plays a critical role in the development of neuropathy in POEMS. Further research is required to establish the exact mechanism and evaluate B6 supplementation.",
  "authors": [
    {
      "affiliations": [
        "Centre for Waldenstrom’s, POEMS Syndrome and Related Conditions, Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK"
      ],
      "name": "Oliver Tomkins"
    },
    {
      "affiliations": [
        "Neurometabolic Unit, University College London Hospitals NHS Foundation Trust National Hospital for Neurology and Neurosurgery, London, UK"
      ],
      "name": "Simon Alexander Samuel Pope"
    },
    {
      "affiliations": [
        "University College London Great Ormond Street Institute of Child Health, London, England, UK"
      ],
      "name": "Youssef Khalil"
    },
    {
      "affiliations": [
        "Queen Square Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK"
      ],
      "name": "Shiwen Koay"
    },
    {
      "affiliations": [
        "Centre for Waldenstrom’s, POEMS Syndrome and Related Conditions, Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK"
      ],
      "name": "Jahanzaib Khwaja"
    },
    {
      "affiliations": [
        "Centre for Waldenstrom’s, POEMS Syndrome and Related Conditions, Department of Haematology, University College London Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Jonathan Sive"
    },
    {
      "affiliations": [
        "Centre for Waldenstrom’s, POEMS Syndrome and Related Conditions, Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK"
      ],
      "name": "Shirley D’Sa"
    },
    {
      "affiliations": [
        "UCL Great Ormond Street Institute of Child Health, London, UK"
      ],
      "name": "Philippa B Mills"
    },
    {
      "affiliations": [
        "UCL Great Ormond Street Institute of Child Health, London, UK"
      ],
      "name": "Peter T Clayton"
    },
    {
      "affiliations": [
        "Queen Square Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK"
      ],
      "name": "Michael P Lunn"
    }
  ],
  "title": "Acquired vitamin B6 deficiency in POEMS: a marker of disease activity and cause of neuropathy?",
  "uid": "090c7525-7ebf-5113-8fb3-5e2d497a3e3f"
}